Confocal microscope for imaging of selected locations of the body of a patient

ABSTRACT

A confocal imaging microscope, especially for the cellular imaging of the skin at selected locations, is ergonomic in use, compact, and positionable at the locations thereby providing for patient comfort during imaging. The head ( 28 ) contains an integrated assembly of the optical and mechanical components of the microscope. The assembly includes a main chassis plate ( 82 ). The optical components are mounted principally on one side of the plate while a PC board ( 130 ) is mounted on the opposite side of the plate. The board ( 130 ) mounts the electronic components, including interfaces, a microprocessor ( 222 ), and drivers ( 206, 208, 210 ) for motors ( 105, 106, 108 ) which control scanning and may also control fine positioning of the locations being imaged. The head ( 28 ) is detachable from the arm for manual disposition which is useful when imaging, not only the skin but other tissues, especially for research in investigating living processes at the cellular level.

This application is a Divisional of U.S. patent application Ser. No.10/557,461, filed Nov. 18, 2005, now U.S. Pat No. 7,394,592 which claimspriority to U.S. Provisional Application No. 60/471,911, filed 20 May2003, which is herein incorporated by reference.

The present invention relates to confocal microscopes for the imaging ofselected locations on the body of the patient and especially for thecellular imaging of skin at such locations as well as for the imaging ofother living tissue and biological processes. The present inventionprovides a confocal microscope which is ergonometrically adapted toprovide ease of use by containing the confocal microscope components,both optical and electronic, in an imaging head which is supported forprecise placement of the confocal objective while eliminating the needfor extensive re-orientation of the patient, thereby affording patientcomfort during imaging.

It is a principal feature of the present invention to consolidate theoptical and electronic components of a confocal microscope in compactlyorganized relationship, in an imaging head.

Another feature of the invention is to support the head on a positioningmechanism which provides for improved ergonomics in placing the head atprecise locations against the skin of a patient without requiring thepatient to be re-oriented in an uncomfortable position during imagingprocedures.

It is a still further feature of the invention to support the confocalimaging head on an arm mechanism having a plurality of gimbleconnections providing freedom of displacement and rotation of the headso as to enable precise positioning thereof.

It is a still further feature of the invention to provide for thedisconnection of the head for manual orientation which can facilitateimaging for research and clinical applications and investigation ofcellular morphology and processes at the cellular level in skin andother tissues.

Confocal laser scanning microscopes have been provided, which haveconfocal imaging systems, suitable for imaging of skin and othercellular tissues, and reference may be had to Zavislan and Eastman, U.S.Pat. No. 5,788,639, issued Aug. 4, 1988, for Confocal Microscopes whichmay be hand held. Anderson et al., U.S. Pat. No. 5,880,880, issued Mar.19, 1999 describes a confocal laser scanning microscope in which part ofthe optics are mounted in an arm. Such microscopes require electronicequipment for control and processing of image signals which are locatedseparate and apart from the optics. While satisfactory images areobtainable with such laser scanning confocal microscopes, they have beendifficult to use and may be ergonomically unsatisfactory to theclinician operating the microscope to obtain the images at selectedpositions on a patient.

The present invention provides a confocal microscope in which theoptical and mechanical components are integrated and consolidated so asto provide an imaging head which is easy to position and has ergonomicswhich are desirable by clinicians. The head may be used withoutrequiring the patient to be re-oriented with respect to the head inpositions which may be uncomfortable for the patient.

Briefly described, a confocal microscope imaging head in accordance withthe invention enables scanning of precise locations of the body of thepatient and obtaining images of the skin and other tissue whileconsolidating the imaging and control electronics and the opticalcomponents of the microscope into a compact imaging head which isreadily movable by the clinician. The head may have a main chassisplate, on opposite sides of which principal optical components of themicroscope and electronic components may be mounted. The plate alsosupplies a support for the mechanism for fine positioning of theobjective of the microscope, both in focus and laterally. Theelectronics of the head may be mounted on a printed circuit boardattached adjacent to the chassis plate on one side thereof. The head maybe mounted on a multi-axis compound arm having gimbals at joints betweenthe arm segments, and where the arm is connected to an upright stationon which a monitor (display) and a computer on which a keyboard forprogramming and operating the electronics of the head, may be mounted.

The foregoing and other features and advantages of the invention willbecome more apparent from a reading of the following description inconnection with the accompanying drawings in which;

FIG. 1 is a perspective view of an improved laser scanning confocalmicroscope in accordance with the invention;

FIG. 2 is a perspective view of the microscope shown in FIG. 1 takenfrom the top;

FIG. 3 is a perspective view of the imaging head attached to one part ofa multi-axis displaceable and rotatable arm mechanism;

FIG. 4 is an elevational view illustrating the head and the multi-axisarticulated arm mechanism showing positioning of the head both indisplacement and in rotation;

FIG. 5 is a plan view of the head and arm mechanism shown in FIG. 4;

FIG. 6 is a perspective, side view of the head showing the headconnected to the arm mechanism by a detachable connection;

FIG. 7 is a view similar to FIG. 6 showing the head detached from thearm mechanism;

FIG. 8 is a plan view illustrating the ray paths of the beams in thehead of the confocal microscope shown in the preceding figures;

FIG. 9 is a simplified perspective view showing the optical componentsand PCB for mounting the electronic components, with the mountingchassis plate removed so as to more clearly illustrate the PCB and theoptical components;

FIG. 10 is a perspective view illustrating the components of the imaginghead including the objective lens and the mounting thereof to thechassis plate, from which the tubular nose structure surrounding theobjective lens for fine positioning of the skin with respect to theobjective omitted, to simplify the illustration;

FIG. 11 is a perspective view similar to FIG. 10 but showing the tubularnose surrounding the objective lens and the stage for positioning thenose so as to locate the precise position of the skin being imaged, aportion of the mounting plate for the objective lens and the stage onwhich the nose is mounted being cut away along the line 11-11 in FIG. 10to more clearly illustrate the mechanism for adjusting the stage andthereby adjusting the nose and precisely positioning the skin withrespect to the objective;

FIG. 12 is a sectional view taken along the line 12-12 in FIG. 6;

FIG. 13 is a sectional view taken along the line 13-13 in FIG. 7; and

FIGS. 14 and 15 connected as shown in FIG. 16 is a block diagram of theelectronics of the imaging head.

Referring more particularly to FIGS. 1, 2 and 3, there is shown anupright station 10 preferably mounted on casters 12 for movement alongthe floor as by manually gripping and pushing or pulling a bar 14.Shelves 16 and 18, one of which 16 may be above a drawer 20, areconnected between uprights of the station 10. A flat panel monitor, andpersonal computer (PC) 26 may be placed on the lower shelf 18. Thedisplay 22 works with the computer 26 and also provides the images takenby the confocal microscope.

An imaging head 28 is gimble mounted on a multi-axis arm mechanism 30having front and rear arms 32 and 34. The head 28 is removable at acoupling 36 on the free end of the front arm 32. The head 28 has a nose38, preferably made of clear plastic, which is attached to a conical hub40 on the front of the head 28. Handles 42 are manually grasped andmoved to permit multi-axis movement of the head to bring the nose intocontact with the skin of a patient or with other tissue to be imaged.The multi-axis movement is vertical, horizontal and rotational aboutgimble joints 44 and 46 at the rear end of the rear arm 34 and the frontend of the front arm 32. A coupling joint 48 enables rotation of the arm32 with respect to the arm 34. The multi-axis movement of the arms andthe head 28 will be more apparent from FIGS. 4 and 5. There are cablesfrom the head 28 to the PC 26 and between the PC, the monitor and thekeyboard 24. These cables are not shown in the figures to simplify theillustration.

A control panel 50 on the side of the head 28 has two sets of controls52 and 54. The controls 52 facilitate motion of the nose 38 in X and Y(orthogonal) directions so as to provide fine or precise positioning ofthe head with respect to the skin.

Control Panel Also has Provision for Capturing Images

In operation, the nose is brought into contact with the skin at thelocation to be imaged. The front end of the nose has a ring of removabledouble-sided adhesive material, the ring being in the circular area 56at the front end of the nose. The nose is then moved in orthogonaldirections and provides fine positioning, over distances much shorterthan obtainable by manually moving the head through the use of themulti-axis, articulated arm mechanism 30. The location of the section onor internally of the skin location to be imaged is controllable by thecontrols 54, which cause the objective lens to move along the opticalaxis, out of and into the nose. Thus, the exact sections and the exactlocations of the tissue of the body desired to be imaged is imaged.

The multi-axis movement of the head 28 will be more apparent from FIGS.4 and 5. The gimble joints 44 and 46 enable rotational as well asvertical movement. The rotational movement is shown by arrows at the endof the dashed circle 60, 62 and 64 and the up and down movement orrotation about the gimbles 44 and 46 is shown by the arrows at the endof the dashed lines 66 and 68. The gimbles may be spring-loaded or havesufficient friction to enable the arms to stay in the position to whichthey are moved after the head 28 is located.

The detachability of the head 28 from the arms 30 may be obtained by alatch mechanism 70 in a receptacle 72 in the handle 42 (see also FIG.6). When the latch 70 is released, the head 28 held by handles 42 may bemoved and oriented manually, separately from the arm mechanism 30. Thisreceptacle and mechanism is also illustrated in FIGS. 12 and 13.

FIGS. 12 and 13 also show the internals of the confocal microscope headand the bi-part case or housing 80. This case is connected to a mainchassis plate 82. A T-shaped bracket which bridges a polygon scanner 84and presents a rear support plate 86, which provides a firm and solidconnection for the rear of the case 80 and for the handles to the head28. A forward support plate 88, which is connected to the main chassisplate 82 by gussets 90, also has screw holes to which screws (not shown)are inserted so as to attach the parts of the case 80.

The plate 88 also supports an XY stage 92 to which the nose 38 and itsmounting hub 40 are connected, and are movable via the stage 92 for finepositioning, laterally in X and Y directions.

As shown in FIGS. 10 and 11, an objective lens assembly 96 is alsosupported by the plate 88. The stage 92, as shown in FIG. 11, hasforward and rear plates 100 and 102. Slides 104 allow the movement ofthe forward plate 100 in the Y direction shown by arrow 103, whenactuated by the shaft of a linear stepper motor 105 via an arm 106. Therear plate 102 of the stage 92 is moveable in a direction perpendicularto the movement of the front plate 100. The rear plate 102 is mounted onslides (not shown) attached to the support forward plate 88. A linearstepper motor 106 has a shaft connected via an arm 108 to move the plate102 and objective 38 in the X direction shown by arrow 103.

The objective lens assembly 96 includes an objective lens 116 in a lensbarrel. A tube 112 has cam slots 114. Pins 118 in these slots areconnected via a coupling 120 to the objective lens 116. When the tube 96is rotated by a motor 122 via a pinion 124 and ring gear (not shown)around the periphery of the tube 96, the cam slots cause the pins totranslate forward or backward, depending upon the direction of therotation of the motor 122, thereby moving the objective 116 forward andbackwards along its optical axis so as to focus the objective at thesection of the tissue to be imaged.

A barrel inside of the rotating tube 112 contains a pair of compoundlenses 131 and 132 forms part of a forward telescope lens 134. Theforward telescope 134 is assembled inside the rotatable tube 112 of theobjective lens focusing mechanism. The later mechanism is shown in FIGS.10 and 11. A finger 127 on the rotating tube 112 may be used inconjunction with an opto photosensor (not shown) to indicate to theelectronics the location in the direction of the arrows 129 (FIG. 10) ofthe objective 116.

FIG. 8 shows the optical components of the confocal microscope head 28.It will be apparent from FIG. 8 and FIG. 9 and also from the location ofthese components in FIGS. 10 and 11 that the components are principallyon the upper side of the mounting plate 82 and their connected thereto.FIGS. 9, 10 and 11 also show a printed circuit board (PCB) 130 which isattached in parallel spaced relationship to the underside of themounting plate 82; the spacing being afforded by spacers 132.Substantially all of the electronic components are mounted on the PCB130. These components will be discussed in connection with the circuitdiagram (FIGS. 14 and 15).

The optical components of the confocal microscope are the compoundlenses 131 and 132 of the telescope 134, the objective 116 and thepolygon 84 which have already be mentioned. The other components are alaser 140 having a folding mirror 142. A beam splitter 148 is in thepath of the light to the reflecting facets of the polygon 84. Thepolygon may have a multiplicity (say 36) facets. The facets providesuccessive scan lines of the image being formed.

Two compound lenses 150 and 152 form a second telescope which confinesthe beam and is bent in a telescope fold mirror. A galvanometer 156deflects the beam in a cross scan direction so as to displace the scanlines of the image. The beam then passes through the telescope 134 andthe objective 116. The beam is focused by the objective lens and thenreflected from the section of the tissue (patients body location), beingimaged, back through the objective 116, the telescope 134, thegalvanometer 156 mirror, the fold mirror 155, the second telescope 154and the polygon facet, then de-scanning the line, to the beam splitter148. The beam splitter 148 directs the beam to a confocal pinholeaperture 160 of a pinhole detector assembly 162. This assembly includesthe detector which may be an avalanche photodiode and electronicsmounted on a board for developing a video signal corresponding to theimage. This video signal is carried by a cable not shown via connectors164 and 166 on the detector modular 162 and the PC board 130 forprocessing via electronics on the board 130 into an image-formingsignal. This signal is carried by a connector 168 on the PCB 130 via acable (not shown) to the PC for providing the image on the display 22.The signal may be transmitted for telepathological observation at remotepoints or the image printed using a high-resolution (megapixel) printer.

The return beam from the beam splitter 148 is focused on the pinholeaperture 160 by a pinhole lens 170 and a fold mirror 172.

It is the feature of the invention to provide compactness optics as wellas location thereof in essentially the same plane on the upper surfaceof the main chassis support plate. This end is obtained by thearrangement of the optical components so that the beam in the part ofthe optical path between galvanometer and the polygon 84 (principally inthe confines of the second telescope lens 154) crosses the beam in thereturn path from the beam splitter 148 to the pinhole aperture 160. Thebeam portions cross at an angle which exceeds a minimum angle, therebyavoiding any significant interference of the light in the crossingbeams. It will be noted that all the optical components are mounted onthe main chassis plate 82 and almost all are mounted on the uppersurface of that plate.

The photo detector 162 includes a bar 180 which mounts the photodetector on the upper surface of the plate 82. The galvanometer ismounted on a bracket 143 attached to the front support plate 88, so thatgalvanometer-reflecting mirror is in the plane of the optical rays abovethe upper surface of the main chassis plate 88. The polygon 84 is abovethe plate 88. The polygon drive shaft (not shown) for rotating thepolygon 84 extends through the plate 82. A drive motor 182 connected tothe polygon drive shaft may be mounted on the PCB 130.

The circuits on the PCB 130 comprise an imaging laser driver circuit 145for powering the laser 140. This driver circuit includes a laser digitalto analog converter (DAC) 202, and a laser current regulator 204. Thereare three stepper motor drivers 206, 208, and 210 which drive the Xdirection stage drive motor 105, the Y direction stage drive motor 106and the motor 108 which moves the objective lens 116 in the Z direction.There are pixel clock generator circuits 211 including an oscillator 218and a phase lock loop (PLL) frequency synthesizer circuit 220. Amicroprocessor CPU 222 on the board 130 is connected to the DAC 202, andto drivers 206, 208, and 210. The CPU 222 is connected via interfacelines to a field programmable gate array (FPGA) integrated circuit 224.There are image data handling circuits 226, as well as synchronizationserializer logic 228 which primarily reduces the number of physicalconnections between the imaging head 28 and PC 26 so as to allow use ofa non-bulky cable between the two. The deserializer logic 230 alsohandles image formatting in the PC. The polygon motor 84 is speedregulated by a polygon controller circuit 232 which receives a referencespeed signal, in the form of a frequency, from pixel clock throughprogrammable divider 234 on the FPGA. The serializer logic also receivesthe pixel clock through a divider 236 for transmission to PC 26 forimage recovery. Image formation is provided by scanning the outgoinglaser beam onto the tissue sample in raster fashion. The fast axis isproduced by rotating polygon 84 and the slow axis by galvanometer 156.The reflectance properties of the tissue are measured by converting therefracted light, as conditioned by the optics, described on subsequentpages, to a time-varying electronic signal voltage by photodetector 162.This signal is converted to a digital value by analog to digitalconverter 280. A synchronous circuit including line counter and retracelogic 238 drives a galvanometer controller including a digital to analogconverter 240. A galvanometer servo 242 is connected to the galvanometer156. The polygon position is detected by a polygon position (start ofscan—SOS) detector that produces a digital pulse as each consecutivepolygon facet scans the outgoing laser beam across the tissue sample.Line counter and retrace logic 238 counts these SOS edges to control theposition of galvanometer 156. Digital to analog circuit 240 converts theline counter value to an analog voltage that ultimately controls galvo156's angular position. There is a circuit (not shown) for activatingthe monitor 22, there are also register circuits 246 on the FPGAinterface that allow the CPU 222 to programming the various FPGAscanning parameters.

The CPU 222 also receives commands from the head control keyboard 24 onthe casing of the imaging head 28 via a firmware decoder 252 so as tooperate the X, Y and Z motors, 104, 106, and 108, via their drivers.

During operation, firmware directs the microprocessor, using the FPGA224 implemented serializer/deserializer interface 241, to acceptcommands from the host PC via its serial (RS-232) port and from theon-board keypad 24. These commands direct the on-board microprocessor222 to initiate scanning, control laser current, stepper motorpositions, polygon rotational. Programmable divider 234 provides controlof the polygon reference frequency, FPOLY, independently of pixel clock.In doing so, establishes the image's width, in pixels. Likewise, theHPER and VSPER inputs to line counter block 238 establish the displayedimage's height.

In addition to the above-mentioned functions, the microprocessor 222periodically scans its keyboard to detect control activations. Severalfront panel keys have predefined functions that include: starting andstopping imaging (scanning) mode, moving each of three stepper motors,controlling laser operating current (and thereby laser operating power),image capture, image stacking, stacking or sectional imaging asdetermined by which function is currently active. An addition button canbe included to select the active imaging function. This feature can alsobe incorporated into the PC's application program. A brief descriptionof each key function follows.

The command structure allows the host PC to override local controls,and/or obtain the states of local controls at its discretion.

Scan/Stop Scan

A scan/stop scan button directs the microprocessor 222 to initiate ordiscontinue scanning (depending on the current state of scanning), byperforming several related tasks. These tasks consist of programming thepixel clock generating PLL 220 and various FPGA registers 246 (seeMicroprocessor/FPGA interface) according to predefined imagingparameters (such as image width, height and, frame rate), and settingthe laser current DAC to an initial value.

Laser Current Control

As described in subsequent sections, imaging laser power is indirectlycontrolled by laser operating current see (imaging laser driver).

Presses of the increase laser current control cause the microprocessorto increase the laser DAC 202 setting, whereas presses of the decreaselaser current control cause the microprocessor 222 to decrease the laserDAC setting.

Laser current is set to its minimum value during non-scanning periods bythe microprocessor.

X, Y, Z Motor Movement

Three stage positioning stepper motors control imaging depth (Z), andspecimen position (X, Y). These stepper motors 104, 106, 108 arecontrolled by the microprocessor in response to motor movement controls:X+, X−, Y+, Y−, Z+, and Z−. Both fine and course movement modes areavailable that move one step per key activation and multiple steps perkey activation according to the current movement mode (fine or coarse),respectively.

Fine/Coarse Mode Selection

The fine/coarse mode control alternately selects Fine or Coarse movementmode. Microprocessor firmware implements these modes by issuing eitherone, or multiple step commands to the associated motor when itsassociated motor movement control is activated, respectively.

Image Function Selection

There are three imaging modes: image capture, VivaStack® and VivaBlock®.Image capture is simply capturing a single frame from the live videofeed. Sectioning is a series of images, taken at various predefineddepths at the same X, Y location. Stacking is a series of images, takenat the same depth, that are stitched together to form a large areaimage.

The image mode control alternately select between these modes. Thiscontrol's state is relayed to the PC application program for processing.It is the PC 26 application program that implements and organizes thesefunctions.

Imaging Laser Driver

The imaging laser 140 is operated in constant current mode. In thismode, laser power is virtually constant. There is a slight temperatureinfluence on laser power, however, the thermal mass of the laser islarge and the internal operating temperature is fairly constant, thusactual operating power changes are small, typically only 1 or 2%. thusmaintaining virtually constant target signal reflectance (e.g. imagebrightness).

Laser current is regulated by a constant-current load type circuit 204.The constant current load circuit is driven by the DAC 202 whose outputis controlled by the on-board microprocessor 222.

Stepper Motor Drivers

Three PWM mode current regulated motor drivers provide three axismotion, X, Y and focal depth, Z, for the specimen stage 92. The on-boardmicroprocessor 222 in response to front-panel controls 24, positionsthese stages allowing direct operator control of specimen position.

The motor supply voltage is chosen to be considerably higher than themotor ratings so as to produce current slew-rates that are significantlyhigher than they would otherwise be, providing improved step response.The driver circuits 206, 208 and 210 regulate motor current insuring themotors don't overheat. Several current levels are selectable by themicroprocessor allowing the motors to operate at lower current levels tomaintain position at reduced motor power dissipation levels.

Keyboard Multiplexer

The keyboard 24 activates key features and operating modes as well ascontrols motor positions and imaging laser power (via its operatingcurrent). Keyboard status is multiplexed through a serial interface tothe control application program running on the PC 26.

The keyboard 24 is a standard 4×4 row-column multiplexed design and iscontrolled by the on-board microprocessor 222 to allow easy key codeassignment. Decoder 252 is firmware implemented with minimal externalcircuitry provided to accomplish this function.

Pixel Clock Generating PLL

A programmable phase-locked loop frequency synthesizer generates pixelclock (a clock used to sample the imaging digitizer(s) one cycle perpixel). The PLL can generate accurate and stable clock frequencies from5 to 100 MHz.

The PLL 220 is programmed by the microprocessor 222 to generate theappropriate clock frequency based on operator specified image parameters(e.g. width and height).

Dual Imaging Digitizers

In the video image signal digitizer 220, there are two high-speed 10-bitA/D converters 280 and 282 to convert analog reflectance signals from upto two analog signal sources. The first source is the normal reflectancechannel that is proportional to the instantaneous target reflectance andlaser power product. The second detector channel may be sensitive to asecondary illuminating light wavelength, or light property such asfluorescence.

The digital reflectance data is processed within the FPGA 227 andmultiplexed into the outgoing data stream for subsequent display orfurther processing by the PC.

Microprocessor/FPGA Interface

Several functions are implemented within the FPGA 227. Due to itsprogrammable nature, the FPGA can be reconfigured to implementadditional operations.

The microprocessor interfaces to the FPGA with a conventional paralleldata bus. The FPGA is organized as a series of eight, 8-bit controlregisters 246 that are directly accessible by the microprocessor 222.Three address signals from the microprocessor select which FPGA registeris to be accessed. Two additional control signals, R_/W and XFR completethe interface. The level of R_/W controls transfer direction (e.g. databus direction) and XFR acts as a data transfer strobe. This interfacecan be expanded almost indefinitely by defining register selection bitswithin the FPGA logic. That is to say, define a register whose valueselects access to an alternate set(s) of registers.

Imaging Data & Synchronization Serializer Logic

The serializer reduces signal connections between imagingihead 28 andthe PC 26 thereby eliminating the need for bulky cables. The paralleldata signals as well as horizontal and vertical synchronization cyclesare time-division multiplexed. Two data recovery clock signals completethe interface and allow for easy and reliable signal extraction by thedeserializer 230. Numerous data signals can expand the interfacebandwidth as desired at of course the expense of the number of cableconductors.

The deserializer circuitry 230 may be housed in the PC 26 and convertsthe serialized data and control signals back to their original form forpresentation to the video capture board and serial port interfaces inthe PC.

Brushless DC Motor Controller

The rotating polygon 84 implements the high-speed (horizontal) scanningaxis. The outgoing laser beam is swept across the specimen in thehorizontal direction by the moving facets.

The polygon motor may be a three-phase, 120°, brushless DC motor. Acurrent regulating, PWM switched control IC provides basic phasecommutation and current regulation. This IC is part of a secondary speedregulating circuit.

A reference frequency, called F_(POLY), produced within the FPGA(derived from pixel clock), establishes the basic rotational speed forthe polygon motor, and thus the line scan frequency. Since thisfrequency is dependent upon pixel clock (which controls sampling), theratio of these frequencies controls image width. The polygon speedcontroller is a closed-loop feedback servo that acts to regulate motorspeed by comparing the frequency of one hall-effect sensor phase (whoseoutput is two cycles per motor revolution), with a reference frequencynamed F_(poly). The frequencies are converted within the speedcontroller circuitry to DC, ground-referenced voltages that areproportional to motor speed. These voltages are inputs to a traditionalanalog subtracter. The subtracter output is applied to the current inputcontrol of the PWM switched control IC mentioned above, thus forming aproportional closed-loop controller.

Given the forgoing circuit description, the line scan rate is given bythis equation:

$\begin{matrix}{{{Line}\mspace{14mu}{Scan}\mspace{14mu}{Rate}}{\frac{scan\_ line}{\sec} = {{\frac{facets}{revolution} \cdot \frac{1 \cdot {revolution}}{2 \cdot {cycle}} \cdot {f_{poly}({in\_ Hz})}}\frac{cycle}{\sec}}}} & {{Equation}\mspace{20mu} 1}\end{matrix}$Galvanometer Controller

The galvanometer provides the slow-scanning axis positioning mechanism.A line counter, maintained within the FPGA is added to a programmableoffset value. This offset value allows the system to be mechanicallyaligned by the operator and PC keyboard rather than manually movingoptics and mirrors to compensate for manufacturing tolerances. Theresult is fed to the vertical control DAC whose output voltage acts asthe input to a position control, closed-loop servo. The galvanometerprovides an optical position measuring mechanism that provides aground-referenced bipolar output voltage that is proportional to angularposition. The servo 240 drives the galvo coil with the differencebetween the vertical position DAC and measured angular position, thusforming a closed-loop, proportional position control servo.

Polygon Position (SOS) Detector

A secondary laser 244 is swept across a dual-photodetector 245. Acomparitor circuit 247 whose output state is determined by thecomparison of the two detector currents act as a physical start-of-scan(or SOS for short) reference signal. The comparitor is high whenphotodetector A's current is larger then B and low when B is larger thanA's. Also, the exact polarity A>B, B>A only represents a digital signalinversion and is therefore somewhat insignificant. This signal isdigitally delayed within the FPGA to become horizontal sync (HSYNC forshort). Video capture boards synchronize data collection using thissignal, insuring that the imaging laser is located at the same physicallocation for each scanned line.

Field Upoadable Firmware/FPGA Code

The microprocessor 222 has a diagnostic monitor mode that is activatedby applying a specific monitor entry voltage to its IRQ pin andsimultaneously pulsing the reset pin. A circuit is provided that allowsthe FPGA 227 to perform this function thus allowing the host PC toactivate this mode of the microprocessor. During this mode, the externalsystem has access to all registers and memory locations within themicroprocessor's memory map. This mode is used to update themicroprocessor's internal operating program (e.g. firmware) stored inon-board (inside the CPU) flash ROM.

Furthermore, FPGA operating code is stored in a non-volatile serialEEPROM. The microprocessor's I/O signals are directly connected to thereset, clock and data signals of the aforementioned EEPROM. By operatingthese signals in their three-state mode (e.g. by programming them to beinputs to the CPU), they do not interfere with FPGA load operations.Conversely, by placing the FPGA in its reset state, these signals areused to load new programs from microprocessor memory into the FPGAserial EEPROM. After which time, the FPGA can be reset causing it toload the new program data from the serial EEPROM.

From the foregoing description, it will be apparent that there has beenprovided an improved confocal imaging system including a confocalimaging head and associated apparatus. Variations in the system, thehead, and the apparatus, within the scope of the invention, willundoubtedly become apparent to those skilled in the art. Accordingly,the foregoing description should be taken as illustrative and not in alimiting sense.

1. An apparatus for imaging of one or more selected locations of a bodyof a patient comprising: an imaging head having a confocal microscopewith an objective lens having an optical axis, wherein said head has aprojecting nose; an upright support station; a first mechanism attachingsaid head to said support station and providing a multiplicity ofmovements in horizontal and vertical displacement and in rotations ofsaid head to position said head at said one or more selected locations;a second mechanism in said head enabling movement of said nose withrespect to said objective lens in a plurality of directions generallyperpendicular to the optical axis of the objective for fine positioningof said nose precisely at each of said one or more selected locations;and a third mechanism in said head for moving said objective lens inwhich said objective lens is movable by said third mechanism only alongsaid optical axis of said objective lens, wherein said second mechanismand said third mechanism are operable separate from said firstmechanism.
 2. The apparatus according to claim 1 further comprising amanually accessible control panel mounted on said head and havingcontrols for movement of said nose and said objective lens in X, Y and Zdirections, respectively, by said second mechanism and third mechanism,respectively.
 3. The apparatus according to claim 1 further comprising ahandle extending from said head for manually moving said head using saidfirst mechanism to said one or more selected locations.
 4. The apparatusaccording to claim 1 wherein said first mechanism comprises a pluralityof articulated arm sections.
 5. The apparatus according to claim 4wherein said first mechanism further comprises gimble joints whichconnect said arm sections to said support station and to said head, anda joint enabling rotational movement connecting said arm sections toeach other thereby providing said multiplicity of movements.
 6. Theapparatus according to claim 1 wherein said head is disconnectable fromsaid first mechanism for independent movement.
 7. The apparatusaccording to claim 6 wherein said head has a housing and a handle at oneend of said housing providing a receptacle for receiving a connection atan end of said first mechanism in said receptacle in releasably latchedrelationship.
 8. The apparatus according to claim 1 wherein said supportstation provides a platform for mounting a display for monitoring imagesproduced by said confocal microscope.
 9. The apparatus according toclaim 8 further comprising an electronically controllable apparatus forinterfacing with said display and said head to generate confocalmicroscope images of the cellular structure of said body at saidlocations.
 10. The apparatus according to claim 1 wherein said supportstation is mounted on casters for movement thereof with said armmechanism and head across a floor upon which the casters roll.
 11. Theapparatus according to claim 1 wherein said head comprises an integratedmechanical assembly of optical and electronic components for providingsaid confocal microscope.
 12. The apparatus according to claim 11wherein said assembly comprises a PCB (printed circuit board) and achassis plate attached in general parallel relationship, said chassisplate providing a mounting for said optical components, in which saidoptical components mounted to said chassis plate have at least anoptical scanning element, and said PCB providing a mounting for saidelectronic components.
 13. The apparatus according to claim 12 whereinsaid PCB is disposed facing a side of said chassis plate opposite to theoptical scanning element.
 14. The apparatus according to claim 12wherein said PCB has mounted thereon a plurality of circuits forproviding programmed operation and control of said head and creatingsignals providing images of said body at said selected locations. 15.The apparatus according to claim 1 wherein said second mechanism andsaid third mechanism are operable separate from each other.
 16. Aconfocal microscope imaging head comprising an integrated mechanicalassembly of optical and electronic components in a common housing, andwherein said assembly comprises a printed circuit board (PCB) and achassis plate attached in general parallel relationship, said chassisplate providing a mounting for said optical components, in which saidoptical components mounted to said chassis plate have at least anoptical scanning element, and said PCB providing mounting for saidelectronic components, wherein said PCB is disposed facing a side ofsaid chassis plate opposite to the optical scanning element.
 17. Theapparatus according to claim 16 wherein said PCB has mounted thereon aplurality of circuits for providing programmed operation and control ofsaid head and creating signals providing images of selected locations ofsaid body of a patient.
 18. The apparatus according to claim 17 whereinsaid programmed operation has means for providing the ability to upgradefirmware and FPGA (field programmable gate array) program code undersoftware control.
 19. An apparatus for imaging tissue comprising: a headcomprising an projecting nose and imaging means for producing sectionalimages of tissue, said imaging means having optics comprising at leastan objective lens; an upright support station; a first means attachingsaid head to said support station and providing a multiplicity ofmovements in horizontal and vertical displacement and in rotations ofsaid head to position said head in contact with tissue to be imaged; asecond means in said head enabling movement of said nose with respect tosaid objective lens along X and Y orthogonal axes for fine positioningof said nose with respect to said objective lens; and a third means insaid head for moving said objective lens in which said objective lens ismovable by said third means only along a Z axis orthogonal to said X andY axes to enable said imaging means to focus at different depths in thetissue and thereby provide said sectional images at said differentdepths, wherein said first, second, and third means are each operableseparate from each other.